Abstract
PURPOSE: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. In developed countries, intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections are the standard-of-care first-line treatment for DME. However, despite the efficacy of anti-VEGF and associated improvements in prognosis, some patients show only a partial response and continue to require monthly injections. The aim of this study was to investigate the effect of switching from aflibercept 2.0 mg to faricimab (which targets both angiopoietin-2 [Ang-2] and VEGF-A) on visual function, retinal anatomy and intraretinal fluid (IRF) dynamics in patients with refractory DME. METHODS: A single-center, observational study of patients with aflibercept-resistant DME who switched to IVT faricimab treatment, comprising a 3-month loading phase, during which faricimab was administered monthly (total of four injections), followed by a treat-and-extend regimen. Visual acuity, anatomical parameters, and fluid dynamics were assessed from baseline to Month 6 in an interim analysis. RESULTS: Fourteen eyes from 10 patients were included. At Month 6, mean best-corrected visual acuity improved by + 2.7 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (not statistically significant). Mean changes in central macular thickness and outer nuclear layer (ONL) thickness at Month 6 were not significant. However, ONL thickness was significantly reduced in multiples ETDRS macular grid subfields at Month 4. Subretinal fluid volume was negligible through Month 6, with most fluid located in the intraretinal layers (97.8-100%). Total IRF decreased by 22% at Month 4, reaching a nadir of - 37% at Month 2. There was no significant change in mean vascular density from Month 0 to Month 4. CONCLUSION: Faricimab treatment led to modest early improvements in visual acuity and retinal anatomy overall in patients with refractory DME. The reduction in total IRF at Month 4 may be attributable to Ang-2 inhibition in these patients, who had previously not responded to anti-VEGF treatment alone. Longer-term studies are needed to evaluate the durability and long-term efficacy of faricimab for the treatment of refractory DME.